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Impact of ontogeny on linezolid disposition in neonates and infants
Author(s) -
Kearns Gregory L.,
Jungbluth Gail L.,
AbdelRahman Susan M.,
Hopkins Nancy K.,
Welshman Ian R.,
Grzebyk Rosie P.,
Bruss Jon B.,
Anker John N.
Publication year - 2003
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(03)00226-1
Subject(s) - gestational age , pharmacokinetics , medicine , volume of distribution , linezolid , physiology , pediatrics , pregnancy , biology , genetics , vancomycin , bacteria , staphylococcus aureus
The impact of age on linezolid disposition during the first few months of life has not been previously investigated. We characterized linezolid pharmacokinetics after a single, 10.0‐mg/kg intravenous dose in 42 infants stratifiedas follows: group 1 (n = 9), gestational age <34 weeks and postnatal age <8 days; group 2 (n = 7), gestationalage <34 weeks and postnatal age 8 days to 12 weeks; group 3 (n = 11), gestational age ≥34 weeks and postnatal age <8 days; and group 4 (n = 15), gestational age ≥34 weeks and postnatal age 8 days to 12 weeks. Linezolid was quantitated by a validated HPLC–triple‐quadrupole mass spectrometer method from repeated blood samples (n =7, 0.3 mL each) obtained over a 12‐hour period. Pharmacokinetic parameters were determined by standard model‐dependent techniques. The values (mean ± SD) for total body clearance (CL) (0.25 ± 0.12 L · h −1 · kg −1 ), apparent volume of distribution (VD ss ) (0.75 ± 0.19 L/kg), and elimination half‐life (t 1/2 ) (2.8 ± 2.1 hours) from the entire study cohort were similar to values reported previously for children and adolescents. Examination of the linezolid pharmacokinetics as a function of age revealed that CL increased rapidly during the first week of life and as a function of postnatal age. Age stratification revealed lower values for CL in those infants aged less than 8 days (group 1, 0.12 ± 0.06 L · h −1 · kg −1 ; group 3, 0.23 ± 0.12 L · h −1 · kg −1 ) as compared with those aged 8 days to 12 weeks (group 2, 0.31 ± 0.07 L · h −1 · kg −1 ; group 4, 0.31 ± 0.10 L · h −1 · kg −1 ). In contrast to the results for CL, gestational age served to be the most useful predictor of VD ss . Evaluation of the pharmacokinetic data would appear to support the use of linezolid dosing regimens currently approved for infants and young children in neonates with postnatal age greater than 7 days. Clinical Pharmacology & Therapeutics (2003) 74 , 413–422; doi: 10.1016/S0009‐9236(03)00226‐1